Method of making novocaine



Patented July 15, 1924.

UNITED STATES 1,501,635 PATENT' OFFICE.

WIIJIJIAM A. VAN WINKLE, OF MIDLAND, MICHIGAN, ASSIGNOR TO THE DOW CHEMI- CAL COMPANY, OF MIDLAND, MICHIGAN, A CORPORATION OF MICHIGAN.

METHOD OF MAKING NOVOCAINE.

No Drawing.

' IVINKLE, a citizen of the United States, and

v patents there cited involves the reduction of a resident of Midland, county of Midland, and State of Michigan, have invented a new and useful Improvement in Methods of Making N ovocaine, of which the following is a specification, the principle of the invention being herein explained and the best mode in which I have contemplated applying that principle, so as to distinguish it from other inventions.

Various alkamine esters of para-aminobenzoic acid have come into use as local anaesthetics, the most widely used and valu-' able one being the hydrochloride of the diethylamine derivative of ethyl paraaminobenzoate, known to the trade as novocaine or latterly as procaine, this compound having the formula:

NH, \-COOCH,CHN(C,H5);,HC1.5

The preferred method of making novocaine as described in Mays Chemistry of Synthetic Drugs (see p. 102) and in various the intermediate product diethylaminoethyl ester of para-nitrobenzoic acid with tin and hydrochloric acid, as indicated by the following equation:

ticularly pointed out in the claims, the following description setting forth but one of various ways in which the principle of the invention may be used. a

The ester which constitutes the intermediate product above referred to is soluble in acidulated water, and then Application filed March 31, 1920. Serial No. 370,280.

in water and accordingly readily lends itself to electrolytic treatment. In such treatment I preferably acidify the solution by adding a mineral acid, for example sulphuric acid, from ten to twelve per cent of said ester being added .to a twenty-five per cent acid solution. I also preferably add a catalytic agent, for example stannous chloride, a small amount of such agent being suflicient. Thus in practice I employ not to exceed onehadlf of one per cent of such stannous chlor1 e.

The anode used is preferably composed of'sheet lead, while the cathode is of nickel, and a current having a potential of from three to five volts is employed. The electrolysis should be carried on at ordinary room temperature whereupon the reduction proceeds easily and quickly, giving the desired amino-compound exactl as in the equation above presented to illustrate the reaction where tin and hydrochloric acid are employed. The electrodes are unaffected by the reaction except that the tin plates out on the cathode, and oxide forms on the anode, but neither is detrimental to operation. I A diaphragm of suitable acid-resistant material is of course interposed between such electrodes, the foregoing solution of ester, acid and stannous chloride constituting the catholdyte, while a dilute solution of a mineral aci such as sulphuric acid, constitutes the anolyte.

Other modes of applying the principle of my invention may be employed instead of the one explained,-change bein' made as regards the method herein disc osed, provided the step or steps stated by any of the following claims or the equivalent of such stated step or steps be employed.

I therefore particularly point out and distinctly claim as my invention 1. In the manufacture of novocaine, the method of reducing the intermediate diethylaminoethyl ester of para-nitrobenzoic acid, which consists in treating the same electrolytically, substantially as described.

2. In the manufacture of novocaine, the method of reducing the intermediate diethylaminoethyl ester of para-nitrobenzoic acid, which consists in dissolving the same passing an electric current therethrough. I

3, In the manufacture of novocaine, the

method of reducing the intermediate diethylaminoethyl ester of para-nitrobenzoic acid, which consists in dissolving the same in acidulated Water containing a small quantity of a suitable catalytic agent, and then passing an electric current therethrough.

4. In the manufacture of novocaine, the method of reducing the intermediate diethylaminoethyl ester of para-nitrobenzoic acid, which consists in dissolving the same in Water containing approximately twentyfive per cent of sulphuric acid and a small quantity of stannous chloride, and then passing an electric current therethrough.

5. In the manufacture of novocaine, the method of reducing the intermediate diethylaminoethyl ester of para-nitrobenzoic acid,-which consists in dissolving the same in approximately ten (10) parts of water containing approximately twenty-five per cent of sulphuric acid and not to exceed one half (1}) of one per cent of stannous chloride, and then passing an electric current therethrough.

Signed by me at Midland, Michigan, this 26th day of March,1920. I

WILLIAM A. VAN W'INKLE. 

